In Drosophila, activation of the Toll pathway is controlled by the generation of a cleaved, active, Toll-binding form of spatzle ligand. Proteolytic activation of spatzle ligand lies downstream of several zymogen activation cascades that are initiated by different cues. In dorsal-ventral patterning, localized activation of spz results in ventral nuclear accumulation of dl. During viral and fungal and gram positive bacterial immune challenge, zymogen cascades are activated by extracellular pattern recognition receptors or virulence factor-mediated cleavage of the zymogen persephone (psh). (Adapted from FBrf0091014 and FBrf0223077).